Marcelo Nobrega, M.D. Ph.D.

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Professor

Research Description

Our group is interested in dissecting the architecture and function of genes and their regulatory networks. We investigate how the multiple transcriptional enhancers, repressors, and boundary elements connected to a gene interact and orchestrate the precise tissue-specific and temporal-specific expression pattern of that gene. Understanding this process is critical since it is thought that malfunction of the regulatory program of key genes underlie the cause of several human diseases.

Our main focus in the lab is on the regulation of genes controlling heart development and congenital heart diseases. We focus both on dissecting the cis-regulatory landscape of key transcription factors in the heart – TBX20 andTBX5 – and also pursue genome-wide approaches such as ChIP-seq and RNA-seq to understand the regulatory architecture of the developing heart and localize heart enhancers. We employ other experimental tools such as mouse and zebrafish genetic engineering, transgenic reporter assay screens for regulatory potential, comparative genomics and bioinformatics analysis.

A second area of interest in the lab is testing the hypothesis that genome-wide association study (GWAS) hits in non-coding DNA are due to variation within long-range regulatory elements (enhancers or repressors) controlling the expression of nearby genes. Studies interrogating the regulatory landscape of three GWAS loci – intronic regions in TCF7L2 and FTO associated with type two diabetes and obesity, respectively, and a gene desert upstream of MYC associated with numerous cancers – are currently ongoing.